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Signaling pathways and brain structures involved in Nitric Oxide/Dopamine interaction of Sensorimotor gating

Grant number: 11/11449-3
Support Opportunities:Scholarships in Brazil - Post-Doctorate
Effective date (Start): February 01, 2012
Effective date (End): August 31, 2015
Field of knowledge:Biological Sciences - Pharmacology - Neuropsychopharmacology
Principal Investigator:Elaine Aparecida Del Bel Belluz Guimarães
Grantee:Ana Carolina de Castro Issy Pereira
Host Institution: Faculdade de Odontologia de Ribeirão Preto (FORP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated research grant:07/03685-3 - Typical and atypical neurotransmitters in neuropsychiatric disorders, AP.TEM


Schizophrenia is a neuropsychiatric disorder characterized by extensive and complex set of symptoms. It is not the result of a single neurotransmitter dysfunction, but an imbalance between various systems. Cognitive deficits observed in schizophrenia include impairment of the sensorimotor filter, characterized by a deficit of prepulse inhibition (PPI), a predictive model of antipsychotics action. In a similar way, drugs that enhance dopaminergic neurotransmission induce PPI deficit in healthy humans and rodents. On the other hand, evidence of disturbances in the brains of schizophrenic patients in the production and distribution of nitric oxide (NO), a gas that acts as a neurotransmitter / neuromodulator, suggest involvement of this agent in this pathology. The hyperactivity of nitrergic and dopaminergic system could act in parallel on schizophrenia. Our group reported that NO inhibitors, similar to antipsychotics, reverse the deficit caused by psychostimulants amphetamine and methylphenidate in the PPI test. However, it remains unclear the mechanism through which NO acts. The aim of this work is to investigate the signaling systems involved in the interaction between NO / dopamine, through pharmacological tools and a gene silencing system (RNAi). The general objectives are: (i) to investigate the effects of increased NO/cGMP signaling on PPI test and the impact of this condition on dopaminergic manipulation; (ii) to investigate the set of mechanisms that may be involved in effects of NO, such as cyclic nucleotides AMP and GMP and DARPP-32 protein; (iii) to investigate the role of accumbens nucleus on NO/dopamine interaction through RNAi designed complementary to calmodulin 1 protein, limiting step for NO synthesis, or NO neuronial enzyme.

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
ISSY, ANA CAROLINA; DOS-SANTOS-PEREIRA, MAURICIO; CORDEIRO PEDRAZZI, JOAO FRANCISCO; CUSSA KUBRUSLY, REGINA CELIA; DEL-BEL, ELAINE. The role of striatum and prefrontal cortex in the prevention of amphetamine-induced schizophrenia-like effects mediated by nitric oxide compounds. PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY, v. 86, p. 353-362, . (12/17626-7, 11/11449-3)

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